Neisseria gonorrhoeae is responsible for a wide variety of common and important infections such a urethritis, cervicitis, pelvic inflammatory disease and disseminated gonococcal infection. Approximately 400,000 cases of gonorrhea are reported yearly in the USA. The hallmark of a symptomatic gonorrhea is an intense inflammatory response characterized by an influx of neutrophils at the site of infection. The oxidative burst is one of the mechanisms used by neutrophils to kill bacteria. This is characterized by formation of toxic oxygen radicals and H202. It is hypothesized that gonococci use catalase as a mechanism of protection against H2O2 released by PMNs during phagocytosis. Proteins involved in DNA repair such as RecA have also been demonstrated to play a role against H2O2 damage in other pathogens. The long-term objective of the proposed research is to further our understanding of the mechanisms by which N. gonorrhoeae persists during infection in the host. Specifically, We are interested in the role of the N. gonorrhoeae kat and recA genes as a mechanism of persistence during host inflammatory response. To create a research tool to achieve this specific objective single kat and recA mutants and a double kat, recA mutant will be constructed. To test the role of these genes in gonococcal survival in vitro, the viability of each mutant will be compared to that of the wild-type strain following exposure to H2O2 and upon incubation with murine neutrophils. To determine the effect of mutations in catalase and RecA on survival in the genital tract, we will use a murine model of gonococcal genital tract infection. In these experiments the duration of infection of mutants and the wild-type strain will be compared following intravaginal inoculation of estradiol-treated mice.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AI010494-03
Application #
6372924
Study Section
Special Emphasis Panel (ZRG1-ALTX-4 (03))
Program Officer
Hernandez, Milton J
Project Start
2001-09-01
Project End
Budget Start
2001-09-01
Budget End
2002-04-15
Support Year
3
Fiscal Year
2001
Total Cost
$15,056
Indirect Cost
Name
Henry M. Jackson Fdn for the Adv Mil/Med
Department
Type
DUNS #
City
Rockville
State
MD
Country
United States
Zip Code
20817